Efficacy and safety of baricitinib in Japanese patients with autoinflammatory type I interferonopathies (NNS/CANDLE, SAVI, And AGS).

Abstract

BACKGROUND:

This study evaluated the efficacy and safety of baricitinib (Janus kinase-1/2 inhibitor), in adult and pediatric Japanese patients with Nakajo-Nishimura syndrome/chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (NNS/CANDLE), stimulator of interferon genes-associated vasculopathy with onset during infancy (SAVI), or Aicardi-Goutières syndrome (AGS).

METHODS:

A Phase 2/3, multicenter, open-label study (NCT04517253) was conducted across 52 weeks. Primary efficacy endpoint assessed the change in mean daily diary score (DDS) from baseline to the end of primary treatment period. Other efficacy endpoints included change in mean DDS to the end of maintenance period, daily corticosteroid use, Physician's Global Assessment of Disease Activity (PGA) scores, and daily symptom-specific score (DSSS) from baseline to primary and maintenance treatment periods. All treatment-emergent adverse events (TEAEs) that occurred postdosing were recorded.

RESULTS:

Overall, 9 patients (5 with NNS, 3 with SAVI, and 1 with AGS) were enrolled; 55.6% were females, mean age was 26 years, and mean corticosteroid use/weight was 0.2 mg/kg. At the end of primary treatment period, mean DDS decreased from baseline in patients with NNS/CANDLE (0.22) and SAVI (0.21) and increased in the patient with AGS (0.07). At the end of maintenance treatment period, mean DDS decreased from baseline in patients with NNS/CANDLE (0.18) and SAVI (0.27) and increased in the patient with AGS (0.04). Mean percent corticosteroid use decreased by 18.4% in 3 out of 5 patients with NNS/CANDLE and 62.9% in 1 out of 3 patients with SAVI. Mean PGA score decreased from baseline in patients with NNS/CANDLE (1.60), SAVI (1.33), and AGS (1.0), and mean DSSS improved from baseline. All patients reported ≥ 1 TEAE. Frequently reported AEs included BK polyomavirus detection (3; 33.3%), increased blood creatine phosphokinase (2; 22.2%), anemia (2; 22.2%), and upper respiratory tract infection (2; 22.2%). Three (33.3%) patients reported serious adverse events, 1 of which was related to study drug. One patient with SAVI died due to intracranial hemorrhage, which was not related to study drug.

CONCLUSION:

Baricitinib may offer a potential therapeutic option for patients with NNS/CANDLE, SAVI, and AGS, with a positive benefit/risk profile in a vulnerable patient population with multiple comorbidities.

TRIAL REGISTRATION:

NLM clinicaltrials.gov, NCT04517253 . Registered 18 August 2020.

• Authors: Nobuo Kanazawa, Taeko Ishii, Yasushi Takita, Atsushi Nishikawa, Ryuta Nishikomori
• Journal: Pediatric rheumatology online journal (Pediatr Rheumatol Online J) Vol. 21 Issue 1 Pg. 38 (Apr 22 2023) ISSN: 1546-0096 [Electronic] England
• PMID: 37087470 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study)
• Copyright: © 2023. The Author(s).

Chemical References

• baricitinib
• Janus Kinase Inhibitors
• Interferon Type I
• Glucocorticoids

Topics

• Adult
• Child
• Female
• Humans
• Male
• Autoimmune Diseases of the Nervous System (drug therapy, genetics, immunology)
• East Asian People (genetics)
• Skin Diseases (drug therapy, genetics, immunology)
• Treatment Outcome
• Janus Kinase Inhibitors (therapeutic use)
• Hereditary Autoinflammatory Diseases (drug therapy, genetics, immunology)
• Interferon Type I (genetics, immunology)
• Syndrome
• Lipodystrophy (drug therapy, genetics, immunology)
• Fever
• Vascular Diseases (drug therapy, genetics, immunology)
• Glucocorticoids (adverse effects, therapeutic use)